tbuckley/cabot-search huggingface dataset:
P522: OFF-THE-SHELF CD33 CAR-NK CELL THERAPY FOR RELAPSE/REFRACTORY AML: FIRST-IN-HUMAN, PHASE I TRIAL
Authors: Ruihao Huang, Qin Wen, Xiaoqi Wang, Hongju Yan, Yingying MA, Maihong Wang, Xiao Han, Jia Liu, LI Gao, Lei Gao, Cheng Zhang, XI Zhang
Journal: HemaSphere (2023)

Background: CD19 CAR-T cell therapy have brough hope to patients with refractory and relapsed (R/R) B cell malignancies. However, the primary result of CAR-T therapy for patients with R/R AML remained modest. One of the main challenges is that current targets for myeloid malignancies are either widely expressed on healthy hemopoietic stem cells, represented as CD33, which could cause lasting severe bone marrow depression induced by "on target off tumor" side-effect. Aims: To receive a balance, we design a CD33 CAR to recognize AML cells and using NK cells to replace T cells to eliminate tumor cells and avoided mortal bone marrow depression. Methods: 10 qualified subjects with R/R AML aged between 18 and 65 years-old were enrolled and received round(s) of infusion of anti-CD33 CAR NK cells (6×108, 1.2×109 or 1.8×109 cells per round after the precondition with Fludarabine (30mg/m2) and Cytoxan 300-500mg/m2 for 3 days, determined by tumor burden at baseline. We investigated the response rate and treatment related side-effect after the CAR NK cell infusion and recorded the long-term efficacy. Results: 10 pts have finished efficacy assessment. The median treatment lines patients received were 5 lines (range, 3 to 8). In dose group one, three patients received 3 rounds of CAR NK cells (6×108, 1.2×109 and 1.8×109 cells) with the interval of 7 days. In dose group two, 3 patients received one dose of 1.8 ×109 cells CD33 CAR NK cells. In dose group three, 4 patients received 3 rounds of 1.8 ×109 cells CD33 CAR NK cells with the interval of 7 days. Only one patient developed grade 2 CRS presented as lasting fever for 6 days after infusion and alleviated after one dose 5mg Dexamethasone I.V. Six of ten patients have received MRD- CR at day 28 assessment. Conclusion: Our primary data of the phase I trial have proved the primary efficacy and safety of CD33 CAR NK cells for patients with R/R AML. The efficacy needs expanded samples and longer follow up. Keywords: CD33, Acute myeloid leukemia, Cellular therapy
PB1969: PATIENTS WITH CHRONIC MYELOID LEUKEMIA AND CORONAVIRUS DISEASE 2019 IN THE OMICRON ERA
Authors: Feiyang Qi, Mei Bao, Xiaoshuai Zhang, Shasha Zhao, Wenwen LI, Chenglei Wang, Qian Jiang
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background: Since the SARS-CoV-2 Omicron variant became the predominant virus strain circulating in late 2021, rare data on coronavirus disease 2019 (COVID-19) in patients with chronic myeloid leukemia (CML) in the Omicron era were reported. Aims: We aim to explore the prevalence and severity of COVID-19 cause by Omicron variant and variables associated with them in CML patients during the pandemic. Methods: We performed a cross-sectional survey from 2540 CML patients with age of ≥ 16 years from December 15, 2022, to February 15, 2023 covering the peak of COVID-19 epidemic collected through an online questionnaire. Results: In 2540 respondents, 1425 (56%) were male. The median age was 46 years (interquartile range [IQR], 36–56 years). 1655 (65%) reported they had COVID-19 during this period. Among them, 1554 (94%) were mild COVID-19; 94 (6%), moderate; 7 (0.4%), severe; no critical case or death. 20 (1%) were hospitalized including 3 (0.2%) with mechanical ventilation, and all were discharged within 2-3 weeks. The median length of hospitalization was 5 days (IQR, 5–11 days). In multivariate analyses longer TKI therapy duration was significantly-associated with a lower prevalence of COVID-19 (odds ratio [OR] = 0.98; 95% Confidence Interval [CI], 0.95, 1.00; p = 0.043); however, living in the urban area (OR = 1.6 [1.3-2.1]; p < 0.001) and having family member with COVID-19 (OR = 18.2 [14.8-22.3]; p < 0.001), higher prevalence of COVID-19. Old age (OR = 1.2 [1.0, 2.4]; p = 0.017), having comorbidity(ies) (OR = 1.7 [1.1, 2.7]; p = 0.019), and multi-TKI-resistant patients receiving 3rd generation TKI or investigational agents (OR = 2.2 [1.2, 4.2]; p = 0.011) were significantly-associated with a higher risk of moderate or severe COVID-19. Summary/Conclusion: In conclusion, patients with CML with shorter TKI therapy duration, old age, comorbidity(ies), or multi-TKI-resistant patients with CML receiving 3rd generation TKI or investigational agents had a higher prevalence of COVID-19 or higher risk of moderate or severe disease in the Omicron era. Keywords: Chronic myeloid leukemia, COVID-19, Tyrosine kinase inhibitor
P1301: HIGH-DOSE THERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION AS THE FIRST-LINE THERAPY OF FOLLICULAR LYMPHOMA: RESULTS FROM A PROSPECTIVE SINGLE-CENTER STUDY.
Authors: Nelli Gabeeva, Anna Smolyaninova, Anastasia Belyaeva, Svetlana Tatarnicova, Alla Kovrigina, Darima Badmazhapova, Daria Koroleva, Eduard Gemdzhian, Tatiana Obukhova, Andrey Sudarikov, Evgeniy Zvonkov
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: In most cases, follicular lymphoma (FL), the most common indolent lymphatic tumour, is highly sensitive to immunochemotherapy. The course of the disease is characterized by multiple relapses although overall survival (OS) is high. On the other hand, 20 % of patients have early tumour progression within the first 24 months of therapy (POD24) — they comprise a group with an extremely unfavourable prognosis and low OS. High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is usually used in relapses of FL and is a potentially curative method for 50 % of patients (C.Casulo Biol Blood Marrow Transplant 2018) 2021). The efficacy of ASCT as the first-line therapy of FL, including the effect on POD24, is poorly studied. Aims: To evaluate the efficacy and safety of HDT and ASCT as the first-line therapy of FL Methods: The study included patients aged 18–65 years with grade 1–3A FL t(14;18)+, stage III–IV or stage II + bulky, and at least one criterion for the initiation of treatment (Groupe d’Etude des Lymphomes Folliculaires Criteria). The patients received treatment according to the ‘FL-2015’ protocol: 4 R-CHOP, 2 R-DHAP and BeEAM (bendamustine, etoposide, cytarabine and melphalan) and ASCT. The primary endpoint was the overall response (OR)/ complete remission (CR) rate at the end of the chemotherapy course. Secondary endpoints were 3-year OS, progression-free (PFS) and event-free survival (EFS). Date of analysis: 12 February 2023. Peripheral blood and/or bone marrow of included patients was tested for minimal residual disease (MRD) by IGH-consensus PCR. Results: Since 2015, 35 patients have been included in the analysis: median age was 45 years (24 to 63 years). A total of 86 % of patients had stage IV tumours, 79 % had 3–5 FLIPI factors. After the end of treatment, OR/PR were 93 %/93 %. MRD-negativity was achieved in 96 % of patients. Kaplan-Meier (KM) estimation of 3-year OS, PFS and EFS were 95 %, 91 % and 85 %, respectively; median follow-up was 19 months (found by reverse KM method) (Fig 1 and 2, Tab.). POD24 rate was 3 %. There were no deaths due to early toxicity within 100 days after ASCT. Mortality not associated with relapses within the first 2 years after treatment was 7 %: 2 patients died of coronavirus infection after 16 and 22 months. No cases of secondary malignant tumours were registered. Summary/Conclusion: ASCT following HDT with BeEAM protocol as the first-line therapy in FL is highly effective and can significantly reduce the rate of POD24 and tumour-associated early mortality. Keywords: Chemotherapy toxicity, Autologous hematopoietic stem cell transplantation, Follicular lymphoma
PB1825: IDENTIFYING GENE TARGETS FOR DRUG REPURPOSING TO COUNTER MYELOID LEUKEMIA IN CHILDREN WITH DOWN-SYNDROME (ML-DS)
Authors: Anna-Lena Schmell, Kristof Meier, Oriol Alejo-Valle, Dirk Heckel, Raj Bhayadia, Jan-Henning Klusmann
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Transient abnormal myelopoiesis (TAM) is a preleukemic disorder that affects 30% of newborns with Down syndrome, which can progress to myeloid leukemia (ML-DS). The current lack of effective treatments for TAM is due to limited clinical trials and the high sensitivity of trisomy 21 patients to chemotherapeutic toxicity. Preventing the progression from TAM to ML-DS remains a significant challenge. Aims: Our goal is to identity treatment options to prevent the progression from TAM to ML-DS by repurposing FDA-approved therapeutics. Methods: We created an aggressive TAM-like state in murine hematopoietic cells by overexpressing oncogenes located on chromosome 21 to model the genetic origin of ML-DS. We then conducted CRISPR-Cas9 knockout screens, targeting only genes connected to FDA-approved therapeutics, and integrated these findings with ML-DS cell line data. We used single knockout proliferation assays for validation and compared our results to the currently used treatment. Results: Our approach revealed over 30 candidates, with seven genes found to be directly connected in the same pathway. Patient-derived gene expression data and validation in the murine model and leukemic cell lines led to several promising therapeutics. In vitro drug testing of two drugs yielded particularly promising results, individually and when compared to the current treatment. Summary/Conclusion: Our approach of repurposing existing drug targets has led to the discovery of alternative treatments for TAM patients, advancing our long-term goal of preventing cancer in children with a premalignant state. By focusing on the underlying genetic mechanisms, we have increased treatment options, potentially reducing the toxicity burden for TAM patients. Keywords: Pediatric, AML, Down Syndrome, Acute myeloid leukemia
P412: TRANSCRIPTOMIC CLASSIFICATION, RISK STRATIFICATION AND THERAPY SELECTION IN AML
Authors: Jeppe Severens, Onur Karakaslar, Elena Sánchez- López, Redmar Van den Berg, Hendrik Veelken, Marcel Reinders, Marieke Griffioen, Erik Van den Akker
Journal: HemaSphere (2023)

Background: Subtyping of acute myeloid leukaemia (AML) by the World Health Organization (WHO) and International Consensus Classification (ICC) has made significant progress but is currently genetics-based. Studies have shown that transcriptomics can improve AML stratification, but researchers have yet to perform a large-scale analysis of AML transcriptomics. Aims: Perform a systematic unsupervised analysis of transcriptional AML data to improve classification, risk stratification and therapy selection in AML patients. Methods: We integrated and harmonised mRNAseq data from BEAT, TARGET, TCGA and LEUCEGENE with our in-house LUMC dataset (n=1337) and defined transcriptional AML clusters. In addition, we acquired corresponding data on genetics, survival and ex-vivo drug response. We used this data to update AML classes for our samples to the WHO and ICC 2022 standards and tested for differences in mutation status, outcome and drug sensitivity between the found transcriptional subtypes. Results: We defined 19 transcriptomic clusters, and in addition to known genetic subtypes, the clusters improved AML classification and discovered new subtypes (Figure 1). We found only KMT2A-MLLT1 and KMT2A-MLLT10 to share a gene expression profile with KMT2A-MLLT3, improving the subtyping of KMT2A-rearranged AML. Patients with a CEBPA bZIP mutation-like gene expression had the same favourable outcome, extending the CEBPA mutated subtype. We found four NPM1 and nine AML with myelodysplasia-related changes (AML-MRC) subtypes, further stratifying 65% of the AML patiens in our datatset. Besides (co-)mutation status, maturation stage and overall survival, we demonstrated significant differences in ex-vivo drug response between the new NPM1 and AML-MRC subtypes.Summary/Conclusion: Gene expression profiling gives an unprecedented overview of the landscape of AML and identifies new clinically relevant AML subtypes. We show the importance of transcriptomics for routine AML diagnostics and highlight its potential to benefit AML patients greatly. Keywords: Drug sensitivity, WHO classification, Acute myeloid leukemia, Gene expression profile
PB1903: THE PROGNOSTICATION FACTORS IN DE NOVO AML PATIENTS IN A SINGLE CENTER: DO THEY HAVE DIFFERENCES THAN THE REPORTED DATA?
Authors: Nahla Ibrahim
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Introduction: Few studies have addressed the prognostic factors of acute myeloid leukemia (AML) patients in Saudi Arabia. Aims: This is a retrospective study to analyze the prognostic factors in patients with de novo AML at a single institution, owing to the observation of some differences with the reported findings. Methods: De novo AML patients referred to King Abdulla Medical City were included. The patients had undergone routine evaluations, including complete blood count and differential, hepatic and renal profiles, bone marrow aspiration and biopsy, flow cytometry, and cytogenetic testing. Results: Data from 170 AML patients reviewed. Out of the 170 patients, 26 had acute promyelocytic leukemia (APL) and excluded from the analysis. Nine patients refused to have treatment; the remaining 135 patients received therapy as: 119 had intensive induction therapy (cytarabine/idarubicin as a 3 + 7 protocol for 116 patients and FLAG for 3 patients because of abnormalities found by echocardiography). The remaining 16 patients had received less intensive therapy, mainly a hypomethylating agent (azacytidine). The present analysis was limited to the 119 patients who received intensive induction therapy. For the major cytogenetic categories, 17 of 27 patients with core binding factor leukemia (62.9%) were reassigned to the intermediate (n = 10; 37%) or unfavorable (n = 7; 25.9%) risk group according to the FLT3-ITD and NPM results. Of the 50 cases of normal cytogenetic findings, 2 (4%) were considered unfavorable, 12 (24%), favorable, 30 intermediate (60%), and 6 (12%) unknowns. The median leukemia-free survival was 21.5 months. The median overall survival was 16.4 ± 2.2 months, with a 5-year survival rate of 37.2%. Cox regression analysis revealed that the cytogenetics results (P =.001) and the presence of FLT-3 (P =.03) were independent prognostic factors for relapse-free survival. Summary/Conclusion: The present study revealed some differences in patient age and cytogenetic risk groups, including a younger median age, relevance of core binding factor leukemia, and a greater incidence of monosomies. Keywords: Acute myeloid leukemia, Acute promyelocytic leukemia
P1586: COMPARISON OF FREQUENCY OF TRANSFUSION RELATED COMPLICATIONS IN THALASSEMIC AND NON-THALASSEMIC PATIENTS RECEIVING NON LEUKODEPLETED RED CELL CONCENTRATE.
Authors: Tanzeel Imran, Humera Altaf
Journal: HemaSphere (2023)

Topic: 31. Transfusion medicine Background: Thalassemia is the most prevalent genetic disorder of Pakistan, requiring huge annual budgets to cater for its treatment and associated complications related to conventual treatment modalities. Thalassemia patients require regular blood transfusions depending on their severity status and growth requirement. Because of multi transfusion status, patients are prone to transfusion related complications especially febrile non hemolytic transfusion reactions Aims: Cost effective of selected leukodepletion blood products use to prevent transfusion reactions in thalassemia and non thalassemics patients in developing countries like Pakistan. As universal concept of leukodepletion can’t be applied in developing counties because of cost constraint. The reported incidence of FNHTR were less in thalassemia patients requiring regular transfusion than non-thalassemic patients at Jamila sultana foundation (JSF) and Rawal institute of Health sciences(RIHS). Methods: This is a retrospective study carried out on 987 transfusion depended thalassemic patients at JSF and 350 patients requiring packed RCC due to different surgical and non-surgical interventions at RIHSA from January 2022 till December 2022. The total transfusions were classified into categories depending on demand for leukodepletion status of the PRBC. The clinical indication, blood type requirement and the reaction workup done to rule out the hemolytic reactions were recorded. All the transfusion records along with clinical condition were reviewed and transfusion reaction work up was done for etiology purpose. Results: Transfusion reactions were noted in 25 (2.5%) out of 987 thalassemic patients while only 3 (4,2%) patients developed reaction in general population group(surgical and non-surgical). Leukodepleted blood products both by bed side filtration and buffy coat removal was provided to thalassemic patients on next blood transfusion no further transfusion reaction occurred. Whereas in the general population group 2 out of 3 patients developed reaction even after getting leukodepleted Packed RBCs. This observation raised the possibility of some underlying factors responsible for FHTR. Summary/Conclusion: Universal Leukodepletion is an expensive procedure that developing country can’t offer to all its patient. However it can be offered to selected patients that leaves little burden on existing blood banks budgets. Using bedside filter is a better method for avoiding transfusion reactions. Though in resource limited settings, leukoreduction using the buffy-coat method is also effective in reducing the transfusion reactions. Leukoreduction of transfused blood cellular components in thalassemic patients is helpful in preventing transfusion reactions Keywords: Blood transfusion
Biodegradable piezoelectric skin-wound scaffold
Authors: Ritopa Das, Thinh T. Le, Benjamin Schiff, Meysam T. Chorsi, Jinyoung Park, Priscilla Lam, Andrew Kemerley, Ajayan Mannoor Supran, Amit Eshed, Ngoc Luu, Nikhil G. Menon, Tannin A. Schmidt, Hanzhang Wang, Qian Wu, Mahesh Thirunavukkarasu, Nilanjana Maulik, Thanh D. Nguyen
Journal: Biomaterials (2023)
P1674: PAP SCORE (PALLIATIVE PROGNOSTIC SCORE) ESTIMATES SHORT-TERM SURVIVAL IN A COHORT OF HEMATOLOGICAL PATIENTS
Authors: Davide Facchinelli, Pietro Manno, Leonardo Potenza, Claudio Cartoni, Corinna Greco, Marcello Riva, Anna Varalta, Alberto Tosetto
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: Providing palliative care to Haematological patients regardless of diagnosis and prognosis is a concept emphasized by recent reports from the European Hematology Association (E.H.A.) and the World Health Association (W.H.O.). Accurate prediction of survival is necessary for clinical, organizational, ethical reasons and for planning specific care strategies. Many tools have been validated to help physicians estimate survival. Aims: Palliative Prognostic Score (PaP score) is based on 6 items and is recommended by the European Association of Palliative Care (E.A.P.C.) for its high accuracy in predicting short-term survival in terminal solid cancer patients. However, no information are available about the accuracy of Pap score in patients with hematologic malignancies, as these patients were excluded from the score validation study. This study aimed to assess the feasibility and accuracy of PaP score in prospective a cohort of hematological patients. Methods: The survival prediction based on the PaP score was performed on routinely collected clinical data from patients with aggressive hematological disease admitted at an Italian hospital between January and December 2022. All the multidimensional domains of the score were evaluated, including dyspnea, anorexia, Karnofsky Performance Status score (KPS), Clinical Prediction of Survival (CPS), total WBC and lymphocyte percentage. The patients were categorized in the three different risk groups of PaP score according to their 30-day survival probability: group A, >70%; group B, 30%–70%; group C, <30%. The CPS item was estimated by the physician who was taking care of the patient. Results: 143 patients were enrolled. 78 (54.5%) had high grade lymphoma, (27.3%) 32 acute leukemia and 18 (12.6%) with multiple myeloma. The mean age was 73.5 years (range 20-88). At the 30-days follow-up 41 (28.7%) patients had died. The PaP identified three groups with 30 days actual survival (AS) rates of 88.3% (A group), 50% (B group), and 26% (C group), respectively (figure 1A). The probability of survival between A and B and C group resulted statistically significant (p<0.0001). The observed 30-days probabilities of surviving are in good accordance with those predicted by PaP score, suggesting a good calibration (figure 1B). Summary/Conclusion: These data suggest that the PaP scoring system is a reasonably robust method for prognostication also in hematological patients and can help physicians with advanced care planning (ACP).Figure 1. A. Survival curves according to the PaP score. B. ROC curve at 30 days. The area under the curve is very close to 1 emphasizing the accuracy of the test. Keywords: Supportive care, Quality of life
P1514: MOLNUPIRAVIR COMPARED TO NIRMATRELVIR/RITONAVIR FOR COVID-19 IN HIGH-RISK PATIENTS WITH HAEMATOLOGICAL MALIGNANCY IN EUROPE. A MATCHED-PAIRED ANALYSIS FROM THE EPICOVIDEHA REGISTRY
Authors: Jon Salmanton-García, Francesco Marchesi, Barbora Weinbergerová, Caterina Buquicchio, Natasa Čolović, Jens VAN Praet, Philipp Koehler, Iker Falces-Romero, Francesca Farina, Federico Itri, Alessandra Romano, Livio Pagano, Oliver A. Cornely
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Molnupiravir and nirmatrelvir/ritonavir are antivirals aiming to prevent the development of severe forms of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Nirmatrelvir/ritonavir was authorised in Europe in December 2021. Molnupiravir is not yet licensed in Europe. Molnupiravir may be an alternative to nirmatrelvir/ritonavir, because of less frequent adverse reactions and fewer drug-drug interactions. Little is known about comparative efficacy of the two drugs in patients with haematological malignancy (HM) at high-risk of severe COVID-19. Aims: We aimed to assess the effectiveness of molnupiravir compared to nirmatrelvir/ritonavir in our HM patient cohort. Methods: Clinical data of patients treated either with molnupiravir or nirmatrelvir/ritonavir monotherapies for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched in sex, age (±5 years), baseline HM severity and hospital admission to controls treated with nirmatrelvir/ritonavir. Results: A total of 108 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. Patients under molnupiravir treatment had a higher prevalence of lymphopenia (lymphocytes count <201 cells/µl, n=16, 15%) as compared to those under nirmatrelvir/ritonavir (n=6, 6%, p=0.025). Although a similar proportion of vaccinated patients was observed in both groups (molnupiravir n=73, 68% vs nirmatrelvir/ritonavir n=76, 70%), those under nirmatrelvir/ritonavir more often had received four doses (n=21, 19%) as compared to the ones under molnupiravir (n=4, 4%, p=0.002). Nevertheless, no differences were noted in COVID-19 severity (p=0.736). No statistically significant differences were identified in overall mortality rate (molnupiravir n=8, 7% vs nirmatrelvir/ritonavir n=7, 6%, p=1.0) or in survival probability (d30 p=0.39, d60 p=0.70, d90 p=0.92, last day of follow up p=0.92). In all patients, deaths were either attributed to COVID-19 or the infection contributed to death. Figure 1. Survival probability of patients treated for COVID-19 with molnupiravir vs nirmatrelvir/ritonavir. a) Day 30 b) Day 60c) Day 90 d) Last day of follow up Summary/Conclusion: In high-risk patients with HM and COVID-19, molnupiravir showed a mortality rate comparable to nirmatrelvir/ritonavir in this matched-pair analysis. Molnupiravir appears to be an alternative for COVID-19 treatment. Keywords: Treatment, Hematological malignancy, Treatment-related mortality, COVID-19